Establishment of Histone H3 Methylation on the Inactive X Chromosome Requires Transient Recruitment of Eed-Enx1 Polycomb Group Complexes

• Published in: Developmental cell Vol. 4; no. 4; pp. 481 - 495
• Main Authors: Silva, Jose, Mak, Winifred, Zvetkova, Ilona, Appanah, Ruth, Nesterova, Tatyana B, Webster, Zoe, Peters, Antoine H.F.M, Jenuwein, Thomas, Otte, Arie P, Brockdorff, Neil
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2003
• Subjects: Amino Acid Sequence - genetics; Animals; Cell Differentiation - genetics; Cells, Cultured; Chromatin - genetics; Chromatin - metabolism; DNA Methylation; Dosage Compensation, Genetic; Embryo, Mammalian - embryology; Female; Fetus; Gene Expression Regulation, Developmental - genetics; Histone-Lysine N-Methyltransferase; Histones - genetics; Histones - metabolism; Lysine - genetics; Lysine - metabolism; Male; Methyltransferases - genetics; Methyltransferases - metabolism; Mice; Mice, Inbred C57BL; Polycomb Repressive Complex 2; Polycomb-Group Proteins; Protein Methyltransferases; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA, Long Noncoding; RNA, Untranslated - genetics; RNA, Untranslated - metabolism; Totipotent Stem Cells - cytology; Totipotent Stem Cells - metabolism; X Chromosome - genetics
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/S1534-5807(03)00068-6

Previous studies have implicated the Eed-Enx1 Polycomb group complex in the maintenance of imprinted X inactivation in the trophectoderm lineage in mouse. Here we show that recruitment of Eed-Enx1 to the inactive X chromosome (Xi) also occurs in random X inactivation in the embryo proper. Localization of Eed-Enx1 complexes to Xi occurs very early, at the onset of Xist expression, but then disappears as differentiation and development progress. This transient localization correlates with the presence of high levels of the complex in totipotent cells and during early differentiation stages. Functional analysis demonstrates that Eed-Enx1 is required to establish methylation of histone H3 at lysine 9 and/or lysine 27 on Xi and that this, in turn, is required to stabilize the Xi chromatin structure.